Brent B. Ward

Bisphosphonate-related Osteonecrosis of the Jaw: A Pictorial Review

Bisphosphonate-related osteonecrosis of the jaw (ONJ) is characterized by nonhealing exposed bone in the maxillofacial region in patients who have undergone bisphosphonate treatment. The underlying etiology is unclear and may be multifactorial. The diagnosis is primarily clinical. Diagnostic tissue sampling may exacerbate the process and is typically avoided, necessitating other diagnostic approaches. The appearance of ONJ at diagnostic imaging is variable and includes sclerotic, lytic, or mixed lesions with possible periosteal reaction, pathologic fractures, and extension to soft tissues. There is a spectrum of signal intensity changes on T1- and T2-weighted magnetic resonance (MR) images with variable enhancement, findings that may correspond to the clinical and histopathologic stage of the process. Bone scintigraphy is sensitive with increased uptake in the area of the lesion. Although the imaging findings are nonspecific, there appears to be a role for imaging in the management of ONJ. Radiography is relatively insensitive but typically employed as the first line of radiologic investigation. Computed tomography and MR imaging are more precise in demonstrating the extent of the lesion. A number of imaging modalities have revealed lesions that may be associated with bisphosphonate exposure in asymptomatic individuals or in the context of nonspecific symptoms. The risk of these lesions advancing to overt clinical disease is unknown at this time. The radiologist should be aware of ONJ and include it in the differential diagnosis when evaluating patients with a history of bisphosphonate therapy without jaw irradiation, so as to avoid potentially harmful biopsies.

Endothelial interleukin-6 defines the tumorigenic potential of primary human cancer stem cells.

Head and neck squamous cell carcinomas (HNSCC) contain a small subpopulation of stem cells endowed with unique capacity to generate tumors. These cancer stem cells (CSC) are localized in perivascular niches and rely on crosstalk with endothelial cells for survival and self‐renewal, but the mechanisms involved are unknown. Here, we report that stromal interleukin (IL)−6 defines the tumorigenic capacity of CSC sorted from primary human HNSCC and transplanted into mice. In search for the cellular source of Interleukin‐6 (IL‐6), we observed a direct correlation between IL‐6 levels in tumor‐associated endothelial cells and the tumorigenicity of CSC. In vitro, endothelial cell‐IL‐6 enhanced orosphere formation, p‐STAT3 activation, survival, and self‐renewal of human CSC. Notably, a humanized anti‐IL‐6R antibody (tocilizumab) inhibited primary human CSC‐mediated tumor initiation. Collectively, these data demonstrate that endothelial cell‐secreted IL‐6 defines the tumorigenic potential of CSC, and suggest that HNSCC patients might benefit from therapeutic inhibition of IL‐6/IL‐6R signaling. Stem Cells 2014;32:2845–2857

Osteonecrosis of the jaw: An update and review of recommendations

Bisphosphonates have had a very positive impact as therapeutic agents for cancer and osteoporosis, but have also been associated with osteonecrosis of the jaw (ONJ) which has emerged as an idiosyncratic oral complication. Bisphosphonate-associated ONJ has generated wide attention despite its considerably rare occurrence. Many speculations exist as to why bisphosphonates may increase the incidence of ONJ. The American Society for Bone and Mineral Research established a task force on bisphosphonate-associated ONJ and recently released a summary report of their findings. A case definition delineated a confirmed case of ONJ as ‘an area of exposed bone in the maxillofacial region that did not heal within 8 weeks after identification by a health care provider, in a patient who was receiving or had been exposed to a bisphosphonate and had not had radiation therapy to the craniofacial region’. Treatment recommendations have been developed by the American Dental Association, the American Association of Oral and Maxillofacial Surgeons and the American Society for Bone and Mineral Research. Considering the scientific evidence, little is known about the true incidence and pathophysiology, and many questions persist. New epidemiologic studies are surfacing and attempts to ameliorate the condition may shed light on the likely complex etiology. The bones of the oral cavity provide a unique environment relative to blood flow, oral microbiota, bone structure and function. Although little is known of the mechanisms and course of ONJ, even less is known about the spectrum of issues of altered healing that could fall short of defined ONJ.

Targeted dendrimer chemotherapy in an animal model for head and neck squamous cell carcinoma.

PURPOSE Nanoparticle drug delivery offers a potential solution in the treatment of cancer. Using a heterotopic tumor model for head and neck squamous cell carcinoma (HNSCC), tumors of variable folate binding protein-alpha (FBP-α) have been treated to delineate receptor necessity as well as efficacy and toxicity of folate targeted chemotherapy. MATERIALS AND METHODS University of Michigan Squamous Cell Carcinoma (UM-SCC) and American Type Culture Collection (ATCC) cell lines were screened using quantitative real-time polymerase chain reaction for FBP-α expression. Acetylated generation 5 dendrimers conjugated to the targeting moiety folic acid and the therapeutic moiety methotrexate were fabricated and administered to severe combined immunodeficiency (SCID) CB-17 mice inoculated with UM-SCC-1, UM-SCC-17B, and UM-SCC-22B cancer cells. Mice were injected with targeted therapy, free methotrexate, or saline control and monitored for drug efficacy and toxicity. RESULTS Targeted therapy was effective relative to receptor level expression. Targeted therapy could be delivered in molar doses 3 times that of free drug. The treatment of a high folate expression tumor cell population was noted to have increased efficacy over saline (P < .01) and free methotrexate (P = .03) as well as decreased systemic toxicity. CONCLUSIONS This report represents the first translation of dendrimer-based chemotherapy to HNSCC and underscores its effectiveness as an antitumor agent in human cancer cell lines with lower levels of FBP-α than the in vitro and in vivo models previously reported.

Methicillin-resistant Staphylococcus aureus sinusitis associated with sinus lift bone grafting and dental implants: a case report.

Treatment of the atrophic maxilla with sinus lift bone graft augmentation and endosseous implants has become common practice and enjoys a strong record of success in the treatment of edentulous patients. Sinusitis has been reported as a complication of sinus lift surgery or perforation of the sinuses by implants. We present an unusual case of methicillin-resistant Staphylococcus aureus (MRSA) infection associated with endosseous implants of the sinuses that illustrates a potentially serious complication of this seemingly benign procedure and illustrates the importance of considering implant exposure and infection as a part of the differential diagnosis in sinusitis.

The palatal flap

Considering the wide variety of options for the reconstruction of posttraumatic and postablative intraoral defects, the palatal flap holds many advantages over other forms of reconstruction. It has been used successfully with minimal morbidity for reconstruction of defects within the reach of the flap. The cases presented herein demonstrate the versatility of this flap, which should be part of the armamentarium of the reconstructive surgeon.

Correlating the depth of invasion at specific anatomic locations with the risk for regional metastatic disease to lymph nodes in the neck for oral squamous cell carcinoma

The purpose of this study was to investigate the critical primary tumor depth of invasion in oral squamous cell carcinoma that would lead to a 20% or greater risk of nodal metastasis.

Progress in cancer nanotechnology.

Publisher Summary A strict definition of nanotechnology refers to molecular devices smaller than 100 nm, which are, therefore, on the nano scale. One nanometer (nm) is one billionth or 10–9 of a meter. Nanomedicine has emerged as a specific focus in nanotechnology and refers to medical interventions at the molecular scale for curing disease or repairing damaged tissues such as bone, muscle, or nerve. This field combines the expertise of individuals in medicine, mathematics, biology, engineering, chemistry, and computer science for the creation of devices for human application. While many fields are now employing nanomedicine, the major focus remains in oncology. Potential applications involve the ability to specific targeted treatment of cancer and also enhanced ability for the prevention, early diagnosis, and monitoring of oncologic disease progression through superior imaging techniques. According to the National Cancer Institute, nanotechnology will serve as multifunctional tools that will not only be used with any number of diagnostic and therapeutic agents but will change the very foundations of cancer diagnosis, treatment, and prevention. The envisioned multifunctional smart nanodevice would contain the ability to (a) detect cancer at an early stage, (b) enhance imaging to pinpointing tumor location, (c) deliver drugs effective against the tumor, (d) and allow for monitoring of cancer cell eradication.

Targeted Therapy in Head and Neck Cancer

The desire to target therapies to specific cancers while leaving the host unharmed remains an ongoing quest for scientists, surgeons, radiation oncologists, and medical oncologists. In recent years, great scientific progress has been made in targeted therapies. Although many modalities remain in preclinical validation, some advances affect patient care today. This article summarizes the concepts of targeting and explores current examples of successful targeting and emerging targeting technologies in head and neck oncology.

Maxillary and Mandibular Non-Hodgkin Lymphoma with Concurrent Periapical Endodontic Disease: Diagnosis and Management

Extranodal non-Hodgkin lymphoma (NHL) in the oral region can present similarly to diseases of odontogenic origin. The objective of this report was to describe a rare case of maxillary and mandibular NHL that presented similarly to and concurrently with lesions of odontogenic origin.A unique case of extranodal NHL, which presented at the apices of maxillary and mandibular teeth in conjunction with lesions of odontogenic origin in a 68-year-old white man, is described. The patient sought care because of a lesion in the right maxillary paranasal region that caused him paresthesia. Radiographically, periapical radiolucencies were present along teeth #5-8, #23 and 24, and #30 and 31. Biopsies of the right maxillary and anterior mandibular lesions were completed and led to a diagnosis of NHL at the apices of teeth #5-8 extending to the hard palate and granulation tissue at the apices of teeth #23 and 24. Two years later, the patient returned because of pressure and sensitivity associated with teeth #30 and 31. Vestibular swelling was noted clinically, and a multilocular periapical radiolucency was present radiographically. Via endodontic therapy and a positron emission tomographic scan, the lesion associated with teeth #30 and 31 was determined to be of both odontogenic and nonodontogenic origin because it possessed both a sinus tract associated with tooth #30 and NHL. Lesions of odontogenic and nonodontogenic origin possess diagnostic and treatment challenges because they may present similarly and/or concurrently. Thoughtful and conservative management of odontogenic lesions with associated NHL is imperative. Interprofessional collaboration and communication among providers must be thorough and clear to properly coordinate care and prevent delays in diagnosis and treatment when these entities occur together.